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Size-tuneable and immunocompatible polymer nanocarriers for drug delivery in pancreatic cancer.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Popov, Andrea Bistrović 
Melle, Francesca 
Linnane, Emily 
González-López, Cristina 
Ahmed, Ishtiaq 

Abstract

Nanocarriers have emerged as one of the most promising approaches for drug delivery. Although several nanomaterials have been approved for clinical use, the translation from lab to clinic remains challenging. However, by implementing rational design strategies and using relevant models for their validation, these challenges are being addressed. This work describes the design of novel immunocompatible polymer nanocarriers made of melanin-mimetic polydopamine and Pluronic F127 units. The nanocarrier preparation was conducted under mild conditions, using a highly reproducible method that was tuned to provide a range of particle sizes (<100 nm) without changing the composition of the carrier. A set of in vitro studies were conducted to provide a comprehensive assessment of the effect of carrier size (40, 60 and 100 nm) on immunocompatibility, viability and uptake into different pancreatic cancer cells varying in morphological and phenotypic characteristics. Pancreatic cancer is characterised by poor treatment efficacy and no improvement in patient survival in the last 40 years due to the complex biology of the solid tumour. High intra- and inter-tumoral heterogeneity and a dense tumour microenvironment limit diffusion and therapeutic response. The Pluronic-polydopamine nanocarriers were employed for the delivery of irinotecan active metabolite SN38, which is used in the treatment of pancreatic cancer. Increased antiproliferative effect was observed in all tested cell lines after administration of the drug encapsulated within the carrier, indicating the system's potential as a therapeutic agent for this hard-to-treat cancer.

Description

Keywords

Drug Carriers, Drug Delivery Systems, Histocompatibility, Humans, Nanoparticles, Pancreatic Neoplasms, Polymers, Tumor Microenvironment

Journal Title

Nanoscale

Conference Name

Journal ISSN

2040-3364
2040-3372

Volume Title

14

Publisher

Royal Society of Chemistry
Sponsorship
Engineering and Physical Sciences Research Council (EP/S009000/1)
Cancer Research UK (CB4270)
Medical Research Council (MR/R000530/1)
Cancer Research UK (C62187/A29760)